The National Children's Study (NCS) is prospective longitudinal cohort study of the individual and combined effects of environmental exposures and gene environmental interactions on child health and development in a representative sample of approximately 100,000 children born in the United States. The children will be followed from before birth until age 21. The importance and timeliness of this study are based on many factors, including past experiences demonstrating profound effects of environmental exposures, such as exposures to alcohol during pregnancy and to lead in early childhood on child health and development;the special vulnerabilities of children to environmental exposures compared to adults;known ongoing exposures, such as prevalent levels of non-persistent pesticides or hours of media exposure per day in young children;and evidence for environmental contributions or causes to such high-impact conditions as autism, developmental delay and developmental disability, asthma, and obesity. The primary aim of the NCS is to investigate the separate and combined effects of environmental exposures (chemical, biological, physical, psychosocial) as well as gene-environment interactions on pregnancy outcomes, child health and development, and precursors of adult disease. Unique features of the study include its focus on environmental exposures at the earliest stages of pregnancy (as well as thereafter) and the breadth of planned exposure and outcome measurements. The NCS responds to the Congressional mandate of the Children's Health Act of 2000, that the NICHD and a consortium of federal agencies plan and conduct a longitudinal study of the impacts of environmental exposures on children.